Project description:Set1-mediated methylation of histone H3 at lysine 4 (H3K4) is a well-established marker of active transcription in eukaryotes. However, absence of Set1 did not significantly alter the overall gene expression; interestingly, some genes exhibited enhanced expression in Candida albicans. The present study aimed to elucidate the role of Set1 in transcription of genes that exhibited increased expression levels in its absence. Ideally, these genes should be repressed and activated in response to specific signals. The hypha-specific genes of C. albicans were expressed in the absence of Set1, even without any external activating signals. These inducible genes displayed atypical H3K4 modification patterns. During the initial induction stages, H3K4 methylation was not involved in the rapid and explosive expression of these genes; instead, acetylation of the same residue was involved. H3K4 acetylation significantly increased in the absence of H3K4 methylation, allowing genes that did not receive external transcriptional signals to initiate mRNA expression, leading to morphological changes. With continued exposure to induction signals, the heightened H3K4 acetylation decreased while H3K4 methylation increased in these genes. Thus, inducible genes receive a positive feedback for stable and sustainable expression. In conclusion, Set1 is a key regulator of transcription in response to external environment changes.
Project description:Set1-mediated methylation of histone H3 at lysine 4 (H3K4) is a well-established marker of active transcription in eukaryotes. However, absence of Set1 did not significantly alter the overall gene expression; interestingly, some genes exhibited enhanced expression in Candida albicans. The present study aimed to elucidate the role of Set1 in transcription of genes that exhibited increased expression levels in its absence. Ideally, these genes should be repressed and activated in response to specific signals. The hypha-specific genes of C. albicans were expressed in the absence of Set1, even without any external activating signals. These inducible genes displayed atypical H3K4 modification patterns. During the initial induction stages, H3K4 methylation was not involved in the rapid and explosive expression of these genes; instead, acetylation of the same residue was involved. H3K4 acetylation significantly increased in the absence of H3K4 methylation, allowing genes that did not receive external transcriptional signals to initiate mRNA expression, leading to morphological changes. With continued exposure to induction signals, the heightened H3K4 acetylation decreased while H3K4 methylation increased in these genes. Thus, inducible genes receive a positive feedback for stable and sustainable expression. In conclusion, Set1 is a key regulator of transcription in response to external environment changes.
Project description:Set1-mediated methylation of histone H3 at lysine 4 (H3K4) is a well-established marker of active transcription in eukaryotes. However, absence of Set1 did not significantly alter the overall gene expression; interestingly, some genes exhibited enhanced expression in Candida albicans. The present study aimed to elucidate the role of Set1 in transcription of genes that exhibited increased expression levels in its absence. Ideally, these genes should be repressed and activated in response to specific signals. The hypha-specific genes of C. albicans were expressed in the absence of Set1, even without any external activating signals. These inducible genes displayed atypical H3K4 modification patterns. During the initial induction stages, H3K4 methylation was not involved in the rapid and explosive expression of these genes; instead, acetylation of the same residue was involved. H3K4 acetylation significantly increased in the absence of H3K4 methylation, allowing genes that did not receive external transcriptional signals to initiate mRNA expression, leading to morphological changes. With continued exposure to induction signals, the heightened H3K4 acetylation decreased while H3K4 methylation increased in these genes. Thus, inducible genes receive a positive feedback for stable and sustainable expression. In conclusion, Set1 is a key regulator of transcription in response to external environment changes.
Project description:Hematopoietic stem cells (HSCs) must ensure adequate blood cell production following distinct external stressors. A comprehensive understanding of in vivo heterogeneity and specificity of HSC responses to external stimuli is currently lacking. We performed single-cell RNA sequencing (scRNA-Seq) on functionally validated mouse HSCs and LSK (Lin-, c-Kit+,Sca1+) progenitors after in vivo pharmacological perturbation of niche signals interferon, granulocyte-colony stimulating factor (G-CSF), and prostaglandin. We identified six HSC states that are characterized by enrichment but not exclusive expression of marker genes. External signals induced rapid transitions between HSC states but transcriptional response varied both between external stimulants and within the HSC population for a given perturbation. In contrast to LSK progenitors, HSCs were characterized by a greater link between molecular signatures at baseline and in response to external stressors. Chromatin analysis of unperturbed HSCs and LSKs by scATAC-Seq suggested some HSC-specific, cell intrinsic predispositions to niche signals. We compiled a comprehensive resource of HSC- and LSK progenitor-specific chromatin and transcriptional features that represent determinants of signal receptiveness and regenerative potential during stress hematopoiesis.
Project description:Methylation of histone H3 lysine 4 by the Set1 subunit of COMPASS correlates withactive transcription. Here we show that Set1 levels are regulated by protein degradation in response to multiple signals. Set1 levels are greatly reduced when COMPASS recruitment to genes, H3K4 methylation, or transcription is blocked. The degradation sequences map to N-terminal regions that overlap a previously identified auto-inhibitory domain, as well as the catalytic domain. Truncation mutants of Set1 that cause under- or over-expression produce abnormal H3K4 methylation patterns on transcribed genes. Surprisingly, SAGA-dependent genes are more strongly affected than TFIID-dependent genes, reflecting differences in their chromatin dynamics. We propose that careful tuning of Set1 levels by regulated degradation is critical for establishment and maintenance of proper H3K4 methylation patterns. Genome binding/occupancy profiling of H3K4me2 and H3K4me3 in yeast
Project description:Methylation of histone H3 lysine 4 by the Set1 subunit of COMPASS correlates withactive transcription. Here we show that Set1 levels are regulated by protein degradation in response to multiple signals. Set1 levels are greatly reduced when COMPASS recruitment to genes, H3K4 methylation, or transcription is blocked. The degradation sequences map to N-terminal regions that overlap a previously identified auto-inhibitory domain, as well as the catalytic domain. Truncation mutants of Set1 that cause under- or over-expression produce abnormal H3K4 methylation patterns on transcribed genes. Surprisingly, SAGA-dependent genes are more strongly affected than TFIID-dependent genes, reflecting differences in their chromatin dynamics. We propose that careful tuning of Set1 levels by regulated degradation is critical for establishment and maintenance of proper H3K4 methylation patterns.